The National Marrow Donor Program (NMDP) was established in 1987 to (1) create a registry of volunteer, tissue-typed, unrelated bone marrow donors and (2) facilitate matched unrelated donor marrow transplants through a coordinated circuit of Donor Centers, Collec-tion Centers, and Transplant Centers. As of April 30, 1999, 3.6 million donors were participating in the registry and 8,309 unrelated marrow transplants had been performed, of which 1,181 were for minority patients. In transplant recipients with early graft loss, the best option for therapy is another dose of stem cells from the original marrow donor. Peripheral blood stem cell (PBSC) components, harvested by apheresis of filgrastim-stimulated donors, provide larger numbers of progenitor cells that engraft more rapidly than marrow-derived cells. For these reasons, a protocol involving all participating NMDP Donor Centers was initiated in February 1997 for the acquisition of PBSCs for second transplants. The objectives of the study are (1) to monitor the safety of filgrastim admi-nistration in healthy volunteer donors, (2) to compare the adverse effects of bone marrow versus PBSC donation, and (3) to monitor the outcome of matched unrelated-donor PBSC transplants, including time to engraftment, incidence of GVHD, and disease free and overall survival. As of April 1999, 59 unrelated NMDP donors received filgrastim 10 mg/kg/day SQ for 5 days, followed by apheresis. All donors experienced granulocyte colony-stimulating factor (G-CSF)- induced fatigue, insomnia, bone pain, or headache, although in only 8 percent of donors were these effects considered severe. Peak mean leukocyte counts after filgrastim were 46 + 14 x 10 to the 9th power/L, and postapheresis thrombocytopenia (<100 x 10 to the 9th power/L) occurred in eight donors (14 percent), all of whom underwent two procedures. The mean time to complete recovery from PBSC donation was 1 week, compared with 3 weeks for marrow harvest. Product CD34 content and recipient outcomes, including time to engraftment, GVHD in the recipient, and overall survival have not yet been evaluated. The NIH Marrow Donor Center, a participant in the NMDP, has 47,730 donors on its registry. NIHs 194 unrelated donors have undergone marrow harvest and ten have undergone PBSC donation for NMDP recipients. Sufficient cells for transplant were obtained in one 12 to 18 liter apheresis procedure in eight of these ten cases. Two of ten donors had very poor CD34 cell mobilization responses to G-CSF and needed two consecutive apheresis procedures to collect the requested dose. None of the ten required a central line. Seven of ten donors preferred G-CSF-stimulated apheresis donations to marrow harvest due to the lack of need for anesthesia and hospitalization. The discomfort of the two procedures was considered equivalent. The principal NIH investigators for this national study are in the DTM/CC. Administrative and statistical support for the study is provided by the NMDP National Office. Filgrastim is provided under an IND agreement with Amgen (BB-IND #6821).